It is the long-range purpose of this project to study how various chemical (pollutants, steroids, etc.) and physiological changes (age, pregnancy, etc.) affect xenobiotic metabolism by the body. This laboratory has concentrated its effort on the lung as a target organ for exposure to environmental stresses. The balance between detoxication and possible toxication pathways in lung is being studied using N-demethylation, N-hydroxylation, and N-oxidase and N-demethylase as model systems. The topics of present interest are the following: 1) hormonal and steroid effects on fetal and neonatal microsomal N-oxidase and N-demethylase activities in lung; 2) N-hydroxylation of a primary amine versus O-demethylation of a non-N-containing compound by a purified and reconstituted lung mixed-function oxidase (MFO) P-450-system to see if differences exist which might be linked to the toxicity of the N-hydroxylation reaction; and 3) N-oxidation of secondary and tertiary amines in rabbit liver microsomes and purified enzyme systems to see if two enzymes are involved in these two reactions. Studies in the near future will include the isolation of lung cell types to study localization of xenobiotic metabolism within the lung and to study toxication-detoxication mechanisms of individual cell populations.